Dan Pardi, MS, PhD
Hannah Went
93
Introduction
In our quest to better understand aging and longevity, scientists have discovered that our chronological age—the number of years we've been alive—doesn't always reflect our body's true biological age. Biological age refers to how old our cells, tissues, and organs appear to be, based on a variety of molecular and physiological markers.
The promise of measuring biological age in humans lies in its potential to provide a more accurate assessment of an individual's health status and risk of age-related diseases. By identifying the key biomarkers that contribute to this theoretical idea of “biological aging,” we may have found a strategy that enables us to better identify when targeted strategies to slow down or even reverse the aging process actually work.
As the field of biological age measurement advances, cutting-edge technologies like methylation array-based diagnostics and multi-omic measurements are emerging as powerful tools to quantify and track our biological age. These innovations just may transform the way we approach aging research and empower individuals to take further control of their health and longevity journey by knowing what is actually working for them.
Guest
In this episode of the humanOS Radio podcast, we welcome Hannah Went, a visionary in the realm of longevity and disruptive health technologies. With a lifelong passion for breakthrough innovations that improve the human condition, Hannah's journey began at the University of Kentucky, where she earned her degree in Biology. Her early research internships in cell signaling and cell biology laid the groundwork for her career in integrative medicine.
As the former Director of Research and Content at the International Peptide Society, Hannah recognized a unique opportunity for methylation-based age diagnostics. This insight led her to found TruDiagnostic in 2020, a cutting-edge company specializing in methylation array-based diagnostics for life extension and preventive healthcare. Today, TruDiagnostic serves functional medicine providers worldwide and boasts one of the largest private epigenetic health databases, with over 75,000 patients tested.
Driven by a commitment to research, under Hannah’s leadership, TruDiagnostic has spearheaded over 30 clinical trials exploring the epigenetic methylation changes in longevity and health interventions. Additionally, she shares her wealth of knowledge through Everything Epigenetics, offering valuable insights into how DNA regulation impacts health.
Here, we explore the future of longevity, the power of epigenetics, and the transformative potential of innovative healthcare technologies.
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Transcript
Dan Pardi 00:00
Measuring health is big business. There are literally thousands of tests to measure some aspect of your health, and it's something many people value and spend money on. We want to know our health status and whether some intervention we are dedicated to, whether it's something lifestyle based or even compliance with the medication, is working and worth the money and effort. This is the promise of health measurements. The global biomarker market was valued at fifty billion dollars in two thousand and twenty three and is projected to grow 12 % year over year to a market size of a and four billion dollars by two thousand and twenty eight. So the biomarker business is big. What exactly is a biomarker? Simply put, a biomarker is any characteristic of the body that can be measured and used to assess health and functioning. A biomarker that is used to identify the presence or absence of a disease is more specifically a diagnostic today i got to speak with Hannah Went Co founder of True Diagnostic, a health measurement company that was founded in the year 2021 of the reasons I'm keen to speak with Hannah is because they are at the forefront of research in this field since they began. I see them as a product company, but also a research organization that is responsible for pushing the field forward. The company is involved in over 30 clinical trials with prestigious academic institutions from around the globe in one way or another, exploring ways methylation status and changes associate with disease outcomes, longevity, and even the impact of interventions that hope to positively influence how we age. Under her leadership, True Diagnostic has developed one of the largest private epigenetic health databases globally, which includes data from over 35,000 thousand. Patients additionally, Hannah created Everything Epigenetics, a platform where she shares insights on how DNA regulation impacts health. Her work and contributions to the field have made her a respected voice in discussions around biological age and the potential for its reversal or deceleration. So Hannah, welcome to the show i'm really glad to have the opportunity to speak with you today.
Hannah Went 02:06
Yeah thank you, Dan, for that wonderful introduction i'm excited to chat with you and have your listeners hear all things about Epigenetics as well.
Dan Pardi 02:16
I just mentioned biological age, so let's start here what is the concept of biological age?
Hannah Went 02:24
Yeah, it's a great starting point so the concept of biological age refers to how old a person seems based on more their physiological functioning of their body rather than their chronological age, which is Simply put just the number of years since you were born. It only increases. Whereas this concept of biological age is determined by assessing various biomarkers that reflect the true health and functionality of various organs and systems and think of that as being bidirectional. You can increase that, or you can decrease that, or you can keep it steady throughout a period of time as well. How are you aging due to your environment, your behavior, rather than just that chronological based age? Think you know for a second picture in your mind a group of three people who are all 45 years old. All right when you picture that, I don't know exactly what you see. I don't see one standard face, right because I know some people who are 45 years old can look much older and then some that can look much younger as well. And that's why chronological age really isn't a good biomarker to predict other outcomes that's where aging at some other level and that's really what that biological age is capturing.
Dan Pardi 03:39
What are some limitations of this concept in general?
Hannah Went 03:44
Oh, yeah, there, there. There are a lot of of limitations i would say a list of of limitations that that we can go through depending on how you actually view this concept, variability within the biomarkers. There's no single set of biomarkers that universally defines biological aging and I think that goes back to what even is aging, what's biological aging there are a lot of different theories of how we're actually aging. I actually went to the first inaugural Biomarkers of Aging Consortium at the Buck Institute out in San Francisco last year and I think they'll continue to have this conference every year, which brings together researchers in this space and people from companies like mine True Diagnostic who are trying to capture this process and in a specific pathway and they're bringing in medical doctors as well so healthcare providers that are actually using these biomarkers in clinics, I would say the number one limitation is what does this really mean what are we capturing what are we reversing or deaccelerating to an extent and what does that mean for the future of our health?
Dan Pardi 04:45
Morgan Levine of Yale describes biological age as a latent concept, similar to IQ. With latent concepts, you cannot measure them directly, but you can infer their value based on other things that you can directly measure. In this case, biological age becomes a global score, if you will, that is, quantifying the different inputs into a value that theoretically represents one's biological age. Understanding that, help me understand that this isn't something that we can find in one particular point in the body, or even say that this is the source of biological aging so for listeners, that's an important point to understand as we continue this discussion. But still, even if we can't measure it directly, it can still be of great value as it becomes increasingly predictive of things we care about, like disease, mortality, functioning. So what are some ways that researchers have looked to calculate biological age?
Hannah Went 05:42
Anyone can create a biological age clock where you can enter a certain metric into a formula and get a number. You then need to validate that number, understand how it was trained but on on the flip side, some biological age concepts that we may be very familiar with are things that could include telomere length, DNA, methylation patterns used in epigenetic clocks. There's different levels of various hormones you can use, even cardiovascular health or cognitive functioning, and more. So there's this wide array of biological ages we can capture that maybe a more accurate or precise picture of someone's individual health status and potential longevity compared to that chronological age number.
Dan Pardi 06:26
Yeah, I found that really interesting as I was looking into the subject and learning more about it, that there are many, many different ways to try to create a predictive model that is assessing this theoretical concept of biological age. In fact, my last podcast was with Ankaj Kapahi from the Buck Institute where we talked about I Age, which is a collaboration that he did with Google where they were looking at the fundus of the eye to create a a biological age score which was really exciting to me because imagine the future, you could go to, let's say your ophthalmologist and they would do a fundus scan and be able to give you a fairly accurate picture so yeah, there's lots of different ways to do that. Generally, what would you want to see in any model that was designed to predict biological age and how would you validate that what's the general process like there?
Hannah Went 07:14
When I get Google alerts that have new biological age clocks created or these interventional trials and and sheets, I will ask myself these five questions and if they don't need any of those, I may not read the paper in depth, I may scan it it's just not going to be as interesting to me personally number one, is it published in a peer reviewed journal and is it predictive of all 'cause mortality and morbidity? That I think is really the number one factor, and I know it, it sounds silly not all of these biological age clocks are going to be published in in great journals. You need to have some knowledge about how papers are are published in the review process to really be able to analyze them properly. And then is it predictive of death and disease outcomes, Those two go hand in hand because if it's published, you're going to be able to tell if it's predictive of those health outcomes so that's number one. Number two, does it correlate with quality of life outcomes and not only lifespan, how long you're living on this earth, but essentially health span? So does it correlate with things like brain imaging, for example? Does it correlate with things like facial aging or functional movements as well those are all very important, number. Three is it? Precise if they're accurate, it's getting closer and closer to something that's known, like your chronological age, right so these clocks instead, you want to ask, are they precise and where is the reproducibility data within those actual clocks?
Dan Pardi 08:39
Hannah, let me interject here real quickly. As I mentioned in the introduction, there are thousands of health tests and not all of them have undergone the same standards of validation. It's a huge endeavor to validate a test it takes a lot of time, and if you're trying to figure out how accurate your test is, you typically see how well it lines up with a current gold standard. But these new tests are entering into new grounds, so there might not be a gold standard to compare to. So I appreciate your emphasis on precision, where the results are consistent if you were to sample the same person repeatedly in the day. So that's got to be both challenging but a fascinating part of this field.
Hannah Went 09:18
Well, I think if I can just reply there again, one important thing to note is we're a CLIA certified lab, which is a fancy way of saying we check all the rules and regulations in order to even properly run this testing at our our facility in Lexington, kentucky. Traditional laboratories like if you're going to get your bloods drawn for a hormone panel, CBC, etcetera, and go to LabCorp and Quest, they're gonna be CLIA certified too. But according to CLIA, you can have up to a 20 % variance in your blood based values, which is insane i didn't know this until recently. That goes back to the fact that we need internal data we're measuring internally how precise these markers really are. But even for your standard lab values, I know healthcare providers who will send samples at the same time to different facilities and to the same facility even, but get vastly different numbers. So yeah, that it's pretty fascinating.
Dan Pardi 10:06
Yeah that 20 % variance is enough to be either categorized as healthy or be put on a medication. So that's a big deal. You were going to say a fourth point, and then i rudely interrupted but.
Hannah Went 10:17
No, you're good. This is great conversation there's there's two more number four is, do these markers actually respond to interventions that beneficially affect the aging process or the biology of aging and what I mean by that is these clocks need to be able to respond, but not too much. So they need to change with things like caloric restriction, which have been proven out in animal models to slow down aging. Even things like synolytic therapy as well, things that we actively know should benefit our underlying biology and then the last one is gonna be, does it explain why you're aging, does it give you feedback? And this was one of the limitations previously is a lot of these biological age clocks, they just give you a number and you kind of look at it and you go, I'm older, I'm younger, great, that's that. But now how we're creating these new kind of biological age clocks, we know the components or the factors which may be driving that aging. Thus, we can actually tell you exactly what you need to target.
Dan Pardi 11:10
So you want to see peer reviewed work. If you want to see that a particular test is being used by researchers so that you have replication and adoption. People in the field find your assessment compelling to be using it in their protocols, which require a tremendous amount of effort to get approved. That always gives me more confidence when I'm looking at any sort of biomarker test that's out there. Has that hard work, expensive work, time consuming work been done? We talked about now biological age can be looked at many different ways there's not just one way to do it. What are the leading ways that are currently considered to be gold standard or best practice to assess biological age?
Hannah Went 11:50
The gold standard is by far going to be looking at the DNA methylation or or epigenetic interpretation and and we can talk about that further in depth here soon more people may be familiar with a older golden standard which was telomere link testing at one time. And the only reason I bring that up is because what we realized now in terms of biological aging is that Telomere link only makes up about 2 % of our entire aging variants. Whereas when we're looking at epigenetics and DNA methylation, we're even starting to see upwards of like 80 % in terms of all of health outcomes. Don't get me wrong, 82 % is better than 80 %, but we don't want to solely focus on the telomeres anymore so I I do think epigenetics is the leading way at this time and continues to prove out to be the best way biological age is measured.
Dan Pardi 12:40
So Hannah, if you wouldn't mind, please give our audience a primer on the differences between genetics and epigenetics.
Hannah Went 12:47
Yeah, absolutely so genetics is your hardware you're getting your genes, your nucleotide sequences, 50 % from mom, 50 % from dad, and those are never going to change it's going to be the same in every very single cell type it's the nature make up of your body where with epigenetics, EPI is a Greek prefix it quite literally just means above or on top of we're looking on top of the genome and I call that the software. So your genetics is the hardware, but the software, the epigenetics is really controlling that hardware, that genetics. And for epigenetics, it's going to be different in almost every single cell type. Your genes, your genetics is the same in an eye cell and in a heart cell. But why is your eye your eye and why is your heart your heart if your genes are the same and it's actually because of your epigenetics, the expression of those genes. That's how I like to compare the two. There are a lot of other ways you can compare the differences. Main point being to your genetics aren't gonna be changing your epigenetics are gonna be modifiable. You can actually start to retest your epigenetics and it's that nurture component. It's how is everything you're doing actually affecting you at the epigenomic level? Again, it's about 80 % even higher of our health outcomes where genomics is around 20 %.
Dan Pardi 14:01
I like that analogy of hardware and software. Hardware is your genes. Epigenetics sits above your genes and controls whether this genetic sequence is signaling for the creation of an eye cell or a heart cell. On top of that, it's also something that is influenced by lifestyle, environment, your experiences. As such, your epigenetics will change over your life and this is what is going to determine what genes are expressed and which ones aren't. And we can measure this. So that's our primer on the difference between genetics and epigenetics. And we are interested of course, in measuring epigenetics now as the gold standard for biological age. Let's now talk about the various ways in which epigenetic tests can be performed. How are these biological samples collected, for instance?
Hannah Went 14:54
These samples can be collected in in all sorts of different ways you'll see companies offering a a blood test or a saliva test or even urine there may be a couple other collection processes you can go through as well. I recommend using one that is just going to be blood or a blood spot card. The reason being is because all of these algorithms, like we went to the first point that are published in peer reviewed, noteworthy journals, are going to be created using blood as that tissue type. Secondarily, we want to use blood as a sample type because again, we want to be able to relate this to outcomes how predictive is it of all 'cause mortality and morbidity? And we only have blood biobanks, right we don't have saliva biobanks so we can't follow people across their entire life with DNA from their actual saliva. If someone is listening and you know of a saliva biobank, I would love to know where that is located and and how we can work with them because that would also make for ease of use, but it is just a simple finger prick blood spot card.
Dan Pardi 15:50
Blood spot card if people aren't familiar with that, is that different than getting a blood test?
Hannah Went 15:55
Yeah, absolutely it's super easy you're just pricking your finger with a couple Lancets, maybe even just one. Then it's just probably the size of a quarter. You fill on a little card and you bandage your finger up and and ship that sample back to the lab and you'll get results in about two to three weeks where as if you're getting your larger bloods drawn as we call it, you'll go out to Quest or LabCorp and have someone take a couple of tubes of of blood so this you can actually do in the comfort of your own home.
Dan Pardi 16:19
That does sound a lot more convenient and accessible. That's good. Tell us about the evolution of these tests, where it started and and where we're at now with the field.
Hannah Went 16:30
These clocks have now been around for a little over 10 years and you you hear people say biological age clock and epigenetic clock. What we mean by clock is we're just taking a group of those DNA methylation epigenetic markers and using machine learning to inform us of how predictive we can be of some type of outcome so we're using machine learning AI to create a model. That's what that clock is really entailing. Ten years ago, I wasn't at the conference where Doctor Steve Horvath, who pioneered this field, will probably win a Nobel Prize for his work where he presented that if we look at DNA methylation, it can actually predict chronological age. I wasn't there, but I know people who were and they said that their jaws dropped to the floor because in science you just don't see that correlation. So it's really cool science, right? Those are called first generation clock stand, meaning again, you take a sample, you look at the DNA methylation and we guess your chronological age. That's good for things like forensics to see how old DNA sample is at a crime scene, to see how old refugees are, to see if they can seek asylum so there are use case scenarios for those and at one point that is what you would get from these testing companies. Recently we've made a lot of improvements where we can capture second generation biological age and this is where we use other underlying data. So think clinical lab values, metabolites, proteins, think physical functions, even telomere length for measuring all of that data and using that in the creation of the DNA methylation algorithm or clock to predict something that is truly biological. So really we only want to use second generation clocks moving forward.
Dan Pardi 18:12
I love this story from the First Generation Clock era. Doctor Gregory Hannum, who then went on to create the Hannum Clock, did so serendipitously. He discovered that there was this pesky covariant in his research where his samples kept tracking with age, and he brought this up in a lab meeting on how to resolve this issue but the lab paused and said wow, that's actually really interesting. So correlating with age is interesting, but it isn't exactly what we care about when we're trying to understand biological age, which could differ from chronological age. So the second generation clocks detect biological age better than the first generation clocks, correct?
Hannah Went 18:58
That's absolutely correct i love that you brought up Doctor Gregory Hanham as well he doesn't get enough limelight, as Doctor Steve Horvath does, So I appreciate that you brought him up too.
Dan Pardi 19:05
Yeah, definitely. So we talked about some of the limitations of biological age as a concept. It's like IQ it's a latent variable you can't measure directly. What are some limitations of these epigenetic assessments of biological age?
Hannah Went 19:21
We're still figuring out what they mean. You could go back to the limitations that I mentioned, right? Do do the clocks actually meet this criteria? There's just not a universal way to interpret this data to control QA, QC laboratory process downstream. One thing that's very exciting, Dan, that I might want to mention too is we use Illumina to process all of our samples in the lab. For those who don't know Illumina, they are very large company and have run about 96 % of the entire world's genomes but they basically create the infrastructure, the machinery we can run the samples on to look at DNA methylation, DNA methylation, epigenetics is so new, we're learning so much about it they actually don't know how to interpret that data. And that's a really big flaw is that we can read the data but we don't know how to interpret it. We're actually creating ADNA Methylation Software Analysis Suite at True Diagnostic. Which will be able to be given to other labs and help streamline that process of interpretation. I think that's a really good start there in terms of solving the limitations into how we actually read this data but I think there has to be some type of cohesion, some type of an agreement. That way we can start using this in medical practice, saying follow this regimen or this protocol or try this strategy to start to see changes in this, thus starting to see reversal in all of those age-related diseases and even death.
Dan Pardi 20:45
We mentioned the hallmarks of aging already. Again, these are not necessarily why we age, but they do reliably occur when we age. Do we know if epigenetic measurement is capturing all aspects of these hallmarks?
Hannah Went 21:03
Yeah, great question. Definitely not all of them, unfortunately. So there's definitely incomplete coverage of the aging hallmarks there. These aging hallmarks keep expanding as time goes on i won't be surprised in a couple years if we get a couple more. Like you mentioned, some of the hallmarks of aging include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, dysregulated nutrients sensing, etcetera, etcetera, etcetera. And most biological age tests are only going to be focusing on one or a few areas like the DNA methylation or like the TLA mayor length. Maybe the more important question to start thinking about is how is epigenetics in general actually associated with some of those hallmarks of aging, right can we report out other hallmarks of aging through the lens of epigenetics, the testing itself we're not capturing the entire aging process, right we're very transparent about that or even all of the underlying mechanisms contributing to aging as an individual.
Dan Pardi 21:58
But if we end up with a method to be able to capture components of aging. So epigenetics seem to be able to capture things like nutrient sensing, stem cell exhaustion, mitochondrial activity, which are hallmarks of aging and not as well other hallmarks. At least capturing some is valuable but incomplete. And so this new idea of multi-omics tests is something that you are taking advantage of. Tell us what you're doing with multi-omics.
Hannah Went 22:28
When True Diagnostic was founded back in 2020 we set out on one mission we had just one goal, which was to create the best scientific algorithm or again clock that still analyzes epigenetic patterns to accurately quantify that biological A gene. But we realized this needs to be a second generation clock, right it can't just be a first generation clock so we need an extensive amount of data and there's no better place to go than a Biobank for this so we actually partnered with researchers from Harvard University and their partners, Biobank they have a lot of great longitudinal outcome data over the last 50 years and we were able to collect data from that multi oh, and by multi, oh, I mean interconnected bio data. So you have your genomic layer, your epigenomics, remember your hardware, it's not going to change but then your epigenomics is actually controlling the expression of those genes. You have your transcriptomics, which is going to be your messenger RNA and it's going to talk to your proteins your proteins are going to fold and give off certain metabolites metabolite's going to be another layer and you get that end result of your pheno or your phenomics, so your phenotypic outwards expression levels and what that actually looks like so that process took a long time it took about 3 and a half years to finalize, but last October we launched what we think is the best biological age clock ever created and that's our Omic MH algorithm named after that idea of the multi ohm. And in particular, the layers we included in that were clinical lab values, metabolomics and proteomics as well to really drive that clock creation.
Dan Pardi 24:01
There's nothing that says a biological age test needs to focus in on only one type of measurement. They could take data sources from anywhere to say this is the most predictive algorithm, and that's what these tests seem to be doing so first you have to be able to capture all that data. Now you have AI where you can you have the ability now to create insights and meaning out of massive data pools so this is all great advancements. Let's talk about aging pace. Aging pace is different than true age score. Tell us about what aging pace is.
Hannah Went 24:39
Yeah so the 18 pace, I didn't mention this kind of technique in order to create these clocks, but we would technically call this a third generation clock. So a third generation clock is really using longitudinal data from the same cohort across the time point so this is also called the Dunedin pace algorithm. If you're familiar, it's a study that happened out of Dunedin, New Zealand where they followed about a individuals starting in nineteen seventy nineteen seventy three and they're still studying them today it's a really unique study, one of a kind, I don't know any other longitudinal cohorts that have a 96 % retention rate. So what they did is, is they captured biomarkers and the methylation epigenetics and created this their generation clock that isn't giving you an age like a biological age number, but it's a pace, it's like a speedometer so how quickly are you aging biologically for everyone, chronological year And if it's faster than one, over time you're going to see your biological age clock increase and if it's slower than one, great, over time you're actually going to decrease that larger biological age. So this is really, really good for end of one precision based medicine to give you quicker feedback because it's quite literally telling you like a three to six month running average of what's going on.
Dan Pardi 25:53
In a talk I gave at the Institute for Human Machine Cognition on how to measure health, I depicted a scenario where a 50 year old man got a biological age test and it had him at 52 SO two years older than his chronological age. But he also got an aging pace measurement that is separate from his biological age score and that had him aging at 10 months for every year this individual was doing shift work in their twenties and living a harder lifestyle and aging faster. And because of that, he quantifies as being two years older than what his chronological age is. If he just got that measurement, he might think my health efforts are not really paying off because I'm older. But actually his aging pay score says that he's currently doing things right. So that's super valuable these are two different tests with two different types of value. It's good to look at them both separately. So what are the different tests that true diagnostic offers?
Hannah Went 26:54
We offer two products that the first product is this complete kit. You're getting the Omic M age I mentioned, you're getting the pace you're getting how much you've smoked across your entire lifetime, how much you've consumed alcohol and other aging scores. I recommend people do that one at baseline i think it's important to really capture everything if you can. You want to do it probably every 9 to 12 months or so, but that one is also going to cost the most as well so it's going to be around four ninety nine. The other product we offer is going to be one people can use for a smaller retest window it's called the true age, pace, pace hinting at that includes the deninden pace in our interpretation of telomere link through DNA methylation and epigenetics that may give you certain hints into your senescent cell burden. That's how we really like to interpret it. That's going to be two twenty nine so there is a pretty large cost difference there. You can do that one as frequent as every two to three months to get more feedback on hey is is what I'm doing working, is it not do I maybe need to adjust a a certain regimen here or there. We may actually see a large infrastructure change from alumina before the end of the year so I do imagine these prices going down.
Dan Pardi 28:06
Yeah, that's terrific so you can do these tests more frequently without a cost burden getting in the way. And the more data that you have in yourself, the better in the future, AI could be looking back on your historical data, the more that's there, the more you're able to potentially find insights that might benefit you and change your trajectory going forward so that's great. So ideally with this true age complete, you're going to get your biological age and you're also going to get your aging pace. You can do this once you can do this every 12 months or two years, but it's a longer time interval. Then on an ongoing basis, every three to six months or so, you could do an aging pace measurement if you're keen on looking at these things frequently to capture a narrower window of time to see how you're doing recently. Similar to how hemoglobin A1C captures average blood glucose over a three month period. So for aging pace, how much time is it capturing is it a three month window six month window?
Hannah Went 29:06
Yeah, I would say in between three to six months, I don't think we can tell exactly. We do know it can change and adds as little as eight weeks, especially if you're changing things like diet we just did the Twins diet study that was in the You are What You Eat documentary on Netflix looking at vegan versus omnivore diets and twin pairs and we even saw the Treach pace change over that eight week period too but.
Dan Pardi 29:28
What diet seemed to do better with?
Hannah Went 29:30
Yeah, vegan. Vegan actually did better with some Symphony age interpretation so individual organ systems were slowed down. We weren't controlling for everything. People on the omnivore diet or eating more calories they weren't on healthy omnivore diet, if you will. So the study was designed for that specific purpose, but I think a lot of people interpreted as flaws of the study. What I thought was really interesting though is when you dive into even the individual components of the Omic MH, we could see individual metabolomic and proteomic base changes that are aligned with previous research when it comes to beginning in omnivore diets.
Dan Pardi 30:05
So many of those comparison studies come down to calories, So I bet you mentioned that. But you know, you have to acknowledge that some diets might be easier to consume a calorie neutral or slight calorie deficit diet. So if they're controlled for calories, maybe you'd see less of a difference or even opposite results possibly. But you have to acknowledge that some diets are easier to over consume so I have to keep that in mind. On that note, we have something that can assess our biological age and the pace at which we're aging. We talked about diet. What else is being looked at to influence the results here?
Hannah Went 30:42
We're gonna go with lifestyle factors and stick on those for for a minute or two stress, sleep and physical activity are huge, right they're they're massive those are the big four if you add the diet back on top of it, again, rather intuitive. I think we see massive changes just in those lifestyle factors alone. That's why we have lifestyle healthcare providers that's why we have integrative functional providers who are counseling us on how to live a healthy lifestyle because it's easier said than done. I think that speaks volumes, even though it may not be as exciting to talk about.
Dan Pardi 31:13
The biggest areas of opportunity for people interested in their health is what I call the fundamentals versus exciting new molecules that we think might intervene in our Physiology in a way that does influences but we overlook stuff that is mundane but highly meaningful because we've heard it so many times. But are we actually implementing the standards of guidance in our life and changing our pattern of living can be quite challenging. But it's good to see that for example the diabetes prevention program where they were looking at people that were pre diabetes and their incidence of developing diabetes over a three-year period, they had them either on Metformin or a lifestyle program. Metformin reduced the incidence of diabetes occurring after three years by 31 % that's amazing. Lifestyle was close to 60 %, so pretty much double what you see with these meds. Gotta keep that in mind if.
Hannah Went 32:03
We think about those fundamentals and the mechanism of action by which they follow take caloric restriction for example you're thinking amator inhibition, right what can actually slow the growth down when we get into compounds from a supplement standpoint, we see broccoli extract following almost that mechanism of action it's gonna help reduce inflammation, oxidative stress downstream as well, especially if you're someone who has a lot of oxidative stress already. Same with rose fair trauma, unless there's kind of that antioxidant push and pull, if you will, where we don't want too many but for those people who do qualify, there could be a nice stack you can create there. On top of that, talking about the end tour inhibition is of course rapamycin. I just went to a longevity conference mastermind in New York this past weekend and rapamycin was definitely a massive subject there. But I think at the end of the day, we all agreed this has not been studied in humans, right, which makes the push even further for these aging clots. How do you actually measure the efficacy of these, especially when they're probably not ever going to go through the FDA approval route so there's some clinical trials that we're pushing through here at true diagnostic, one of them including rapamycin. So we can understand how does this affect the epigenome, longevity, lifespan and healthspan too. The field itself is just really underfunded, right the TEAM trial was initiated was either like 9 or 15 years ago. And guess what, we haven't done anything with it. That's a trial looking at metformin and how it affects aging. So that goes without saying that we need more people involved we need standardized large cohort data sets. And sure, something can actually work at the general population level when you're testing it, especially with these compounds. But what it's gonna come down to at the end of the day is your actual epigenetic makeup. Just because everything you're doing is affecting your epigenetic makeup, it's not gonna be the same as the person in the study, even if we agree that we're not changing anything our environment. As a silly example, if we have plants in our house compared to someone else who's in the study who doesn't have plants, it's been shown there's been correlation with more green space reducing epigenetics, right there are always gonna be other factors which may not even be truly considered in that study designer makeup.
Dan Pardi 34:06
So an argument or criticism of epigenetic clocks has been that they're oversensitive to inflammation. We know that acute inflammation response to exercise happens. Have you done any standardization work to see if a person has, let's say, you know, done a hard workout the day before they take your complete test might that alter the results that they get so, you know, let's say they take it again a week later they haven't aged considerably, but you know, do they get a different score?
Hannah Went 34:39
I don't believe that would be a a true concern. People who say, oh, you know, I I consumed a lot of alcohol the night before, would it actually affect my biological agency score right. Obviously it's going to have different markers compared to the the inflammation that you're getting from the exercise. But I think it's been accounted for when you're actually looking at the single kind of probe analysis that makes up these B chips on what we actually run the sample on, there's a lot of QA QC that goes into it. But then additionally, the algorithms are going to account for a lot of that noise so it's not like when we read those methylation markers, we're scanning through them once and saying awesome, let's put it in the algorithm and get the score. You actually get a replication and we're scanning your sample almost five times and it's just not going to pick up on those faster paced changes to lifestyle. It has to be habitual we've seen that in several internal studies as well.
Dan Pardi 35:30
So this is a really fast moving field. We've gone from more singular measurements with just epigenetics to multiomics. Your own algorithm for these tests is regularly updated. I kind of see this like a SAS products, you know where you buy a SAS product, you're paying a subscription and you're getting the latest edition. So you know, if you make changes to the algorithm and a person has already received one of their tests, say a year ago, is that old test updated with the new algorithm?
Hannah Went 36:03
Absolutely we're about to release our new Symphony age with Yale at the age of an 11 different organ systems in a month or so so literally the first person who took true diagnostic test back in 2020 can say, hey, I want that report, take my raw data file and read it through this algorithm or through this lens i would also argue that data is 4 years old, you need a new test altogether we should probably update that anyways but you're exactly right it really is like a SAS product where we can start to update you and that's why it's so important to us to actually measure as many methylation positions as possible on the array, right we measure about 1 2 million. Some other companies may just measure like 10.000 thousand or a hundred thousand, which is still great but to us it allows the expansiveness of reading previous reports in the framework of the question you just asked.
Dan Pardi 36:45
You just mentioned Symphony age, where you're looking at different organ systems and how they might be aging differently so how hard could be a different age calculation than your brain or a kidney? Is this a separate test or is this an upgrade to your algorithm that will be included in your true age complete test?
Hannah Went 37:06
Yeah, it'll be included on top of everything else that we're including so it'll be one that will be there moving forward and then anyone who's taking it previously can upgrade their report too.
Dan Pardi 37:14
Ok. Last question, so of your future forecasting, where do you think this field might be in like 3 to five years?
Hannah Went 37:22
But the additional work we're starting to do with Harvard with epigenetic biomarker proxies, so interpreting other data markers, other points just through this blood sample, just through this price point and it's going to continue to get cheaper. We can report out over 4000 clinical lab values, metabolites and proteins with A1 to one ratio about it's it's not going to be, you know, perfect, but our correlation value is about 9-8.
Dan Pardi 37:43
We can now get a tremendous amount of data on ourselves and this turns out to be its own type of clinical or consumer challenge so either challenge for the doctor, challenge for the the patient, many of these biomarkers we might be unfamiliar with and how is a ractitioner thought to use this information in their clinical ractice? Is some of it just informational and some of it is meant to be actionable?
Hannah Went 38:08
Yeah, the biological aging is definitely additional to what they're already doing, but they should be measuring it if they want to attack that number one risk factor for all 'cause mortality morbidity but I think you're asking particularly about these epigenetic biomarker proxies in the future. And for those, again, it's not going to act as a replacement right away we're going to have to do some accuracy testing there, right? But eventually that's the goal, that it's going to be a replacement. They truly think epigenetics is causing a paradigm shift, not even in the laboratory testing space. I would go to as as far to say, the entire medical field as a whole.
Dan Pardi 38:39
Great. Well, Hannah, thank you. Very impressive to see what your company has been able to accomplish under your leadership. For me, being able to reliably capture a global health measurement like biological age is trying to do is valuable in many ways. It can help test interventions it could help individuals understand how their efforts are paying off. We already know a lot of ways about how to be healthy, but we don't know everything, and this type of test can add meaningfully to move the field forward. So thank you for your work, and thank you for coming on to the show and chatting with me.
Hannah Went 39:16
Yeah thanks, Dan i super appreciate your time and look forward to catching up soon.